Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 87
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-38896332

RESUMO

INTRODUCTION: To offer an extensive retrospective experience on the management of male breast cancer. METHODS: A multicenter retrospective observational cohort study was conducted, including male patients diagnosed with breast cancer (invasive or in situ) in 12 Italian breast units from January 1975 to December 2019. Patients aged 18 years or older were assessed for eligibility. Exclusion criteria were metastatic cancer at diagnosis, previous cancer(s), received neoadjuvant treatment, incomplete data on (neo) adjuvant treatment(s), and/or follow-up data. Data on radiological examinations, demographic characteristics, risk factors, histological features, receptor status, treatments, and follow-up were collected. RESULTS: In a series of 671 male patients with breast cancer assessed for eligibility, 403 (28 in situ and 375 invasive neoplasms) were included in the study. All included patients underwent surgery. The median age at surgery was 63.8 years (IQR 56.1-72.1). In 68% of cases, patients underwent echography, and in 55.1%, a mammography. Most patients were ER and PR positive (63.8%), HER2 negative (80.4%), with high (≥ 20%) Ki67 values (61.3%), and luminal B subtype (51.1%). The 10-year overall survival was 73.6% (95% CI 67.0-79.1) for invasive breast cancer and 90% (95% CI 65.6-97.4) for in situ breast cancer. In patients with invasive breast cancer, at univariable analysis, having a G3 tumor (vs. G1), pT2/3/4 (vs. pT1), pN2/3 (vs. pN0), luminal B subtype with Ki67 ≥ 20% (vs. Luminal A), were significantly associated with a higher risk of death. In multivariable analyses, pT2/3/4 (vs. pT1) remained significantly associated with a higher risk of death (HR 3.14, 95% CI 1.83-5.39), and having a HER2 positive or a triple-negative subtype (vs. Luminal A) was also significantly associated with a higher risk of mortality (HR 4.76, 95% CI 1.26-18.1). CONCLUSION: Male breast cancer is a rare disease, the better understanding of which is necessary for a more effective diagnostic and therapeutic approach.

2.
Oncologist ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37995311

RESUMO

PURPOSE: The aim of this study was to evaluate the prognostic role of p53 immunohistochemical (IHC) expression in a large cohort of patients with hormone receptors (HR)-positive/Her2-negative primary invasive breast cancer. METHODS: Retrospective review of consecutive cases treated at our Breast Unit between 2003 and 2013. Patients were divided into 3 subgroups based on p53 IHC expression: null (0%), low (0.1%-49%), and high (≥50%) p53 expression. RESULTS: A total of 1387 patients were included in the study with a median follow-up of 86 months. After adjusting for age, size, node status, lymphovascular invasion, progesterone, and Ki67 expression, only null p53 immunophenotype was associated with worse disease-free survival (DFS) (OR 1.74, 95% IC, 1.11-2.71, P = .015) and distant recurrence-free survival (DRFS) (OR 1.73, 95% IC, 1.04-2.90, P = .036). Null p53 impacted significantly DFS and DRFS also in patients with early breast cancer. CONCLUSIONS: p53 IHC expression affects survival and, thus can be a valuable tool in the management of patients with HR-positive/Her2-negative breast cancer.

3.
Lancet Oncol ; 19(10): 1385-1393, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30196031

RESUMO

BACKGROUND: We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between the groups and showed non-inferiority of no axillary dissection relative to axillary dissection. The current analysis presents the results of the study after a median follow-up of 9·7 years (IQR 7·8-12·7). METHODS: In this multicentre, randomised, controlled, open-label, non-inferiority, phase 3 trial, participants were recruited from 27 hospitals and cancer centres in nine countries. Eligible women could be of any age with clinical, mammographic, ultrasonographic, or pathological diagnosis of breast cancer with largest lesion diameter of 5 cm or smaller, and one or more metastatic sentinel nodes, all of which were 2 mm or smaller and with no extracapsular extension. Patients were randomly assigned (1:1) before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection using permuted blocks generated by a web-based congruence algorithm, with stratification by centre and menopausal status. The protocol-specified primary endpoint was disease-free survival, analysed in the intention-to-treat population (as randomly assigned). Safety was assessed in all randomly assigned patients who received their allocated treatment (as treated). We did a one-sided test for non-inferiority of no axillary dissection by comparing the observed hazard ratios (HRs) for disease-free survival with a margin of 1·25. This 10-year follow-up analysis was not prespecified in the trial's protocol and thus was not adjusted for multiple, sequential testing. This trial is registered with ClinicalTrials.gov, number NCT00072293. FINDINGS: Between April 1, 2001, and Feb 8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary dissection (n=469) or axillary dissection (n=465). Three patients were ineligible and were excluded from the trial after randomisation. Disease-free survival at 10 years was 76·8% (95% CI 72·5-81·0) in the no axillary dissection group, compared with 74·9% (70·5-79·3) in the axillary dissection group (HR 0·85, 95% CI 0·65-1·11; log-rank p=0·24; p=0·0024 for non-inferiority). Long-term surgical complications included lymphoedema of any grade in 16 (4%) of 453 patients in the no axillary dissection group and 60 (13%) of 447 in the axillary dissection group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection group versus 85 (19%) in the axillary dissection group, and motor neuropathy of any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary dissection group). One serious adverse event (postoperative infection and inflamed axilla requiring hospital admission) was attributed to axillary dissection; the event resolved without sequelae. INTERPRETATION: The findings of the IBCSG 23-01 trial after a median follow-up of 9·7 years (IQR 7·8-12·7) corroborate those obtained at 5 years and are consistent with those of the 10-year follow-up analysis of the Z0011 trial. Together, these findings support the current practice of not doing an axillary dissection when the tumour burden in the sentinel nodes is minimal or moderate in patients with early breast cancer. FUNDING: International Breast Cancer Study Group.


Assuntos
Neoplasias da Mama/cirurgia , Excisão de Linfonodo/métodos , Mastectomia/métodos , Linfonodo Sentinela/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Mastectomia/efeitos adversos , Mastectomia/mortalidade , Micrometástase de Neoplasia , Fatores de Risco , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Fatores de Tempo
4.
Radiol Med ; 121(7): 557-63, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27033475

RESUMO

PURPOSE: Screening mammogram reading volume (SMRV) and total (screening and clinical) mammogram reading volume (TMRV) per year are strongly associated with the radiologist's diagnostic performance in breast cancer screening. The current article reports the prevalence and correlates of a SMRV and a TMRV ≥5000 among Italian breast screening radiologists. MATERIALS AND METHODS: A questionnaire survey was carried out in 2013-2014 by the Italian Group for Mammography Screening (GISMa). The questionnaire included items of information for radiologist's experience-related characteristics and for facility-level factors supposedly associated with SMRV and TMRV. Multivariate analysis was performed using backward stepwise multiple logistic regression models. RESULTS: Data for 235 radiologists from 51 local screening programmes were received. Of the 222 radiologists who were eligible, 133 (59.9 %) reported a SMRV ≥5000 and 163 (73.4 %) a TMRV ≥5000. Multivariate factors positively associated with both characteristics included: the number of years of experience reading mammograms; the percentage of total working time dedicated to breast imaging and breast care; the participation in diagnostic assessment; and the availability of digital tomosynthesis at facility. Full-time dedication to breast imaging and breast care was associated with the highest odds ratio for a SMRV and a TMRV ≥5000, i.e. 11.80 and 46.74, respectively, versus a percentage of time ≤50 %. An early (<2000) year of implementation of the screening programme and the availability of vacuum-assisted biopsy at facility were associated with a SMRV and, respectively, a TMRV ≥5000. CONCLUSIONS: Increasing the proportion of radiologists with full-time dedication to breast imaging and breast care qualified as the most effective approach to improve SMRV and TMRV.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Radiologia , Feminino , Humanos , Itália , Inquéritos e Questionários , Recursos Humanos , Carga de Trabalho
5.
Int J Cancer ; 136(5): E272-81, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25273595

RESUMO

Tumors characterized by an intense ribosome biogenesis often display a more aggressive behavior. Ribosomal RNA (rRNA) synthesis is controlled at several levels, including the epigenetic regulation of the condensation of chromatin portions containing rRNA genes. JHDM1B (Jumonji C histone demethylase 1B) is a histone demethylase able to regulate the accessibility of rRNA genes. In this study, we aimed to define the contribution of JHDM1B expression to the features of breast cancer, a tumor type whose behavior is related to the rate of ribosome biogenesis. We show that, in breast cancer-derived cell lines, the increase in rRNA transcription that follows JHDM1B knock-down is mirrored by an augmented cell proliferation only in p53 compromised cells, while p53 competent cells undergo cellular senescence and death. The latter effect appears to be mediated by a p38-dependent phosphorylation of p53, inducing the expression of p15(Ink4b) and p21(Waf1). In breast cancers, lower JHDM1B expression correlates with an increased size of specifically stained nucleolar organized regions, a morphological parameter directly related to the rate of ribosome biogenesis and with a poorer prognosis. In addition, in tumors lacking the controller function of p53, a lower expression of JHDM1B is associated with an increased tumor size at diagnosis. Altogether, our data indicate that epigenetic activation of rDNA genes induced by JHDM1B depletion is associated with a p53-dependent growth arrest, but may promote cancer cell growth when p53 is lacking.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Proteínas F-Box/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Ribossomos/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Western Blotting , Neoplasias da Mama/mortalidade , Senescência Celular , Proteínas F-Box/antagonistas & inibidores , Proteínas F-Box/genética , Feminino , Humanos , Técnicas Imunoenzimáticas , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/genética , RNA Mensageiro/genética , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética
6.
World J Surg Oncol ; 13: 129, 2015 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-25881039

RESUMO

BACKGROUND: Greater than 50,000 new cases of breast cancer cases were diagnosed in Italy during 2013, with nearly 15,000 women succumbing to the disease. These epidemiological statistics highlight the overwhelming clinical dilemma of breast cancer and emphasize the need for novel therapeutic targets and prevention strategies. Countless studies in the fields of mammary gland development and breast cancer have led to an appreciation of a breast tumor microenvironment that actively contributes to the heterogeneous nature of breast cancer. METHODS: The current review will focus on the impact of IL-6 and in the breast tumor microenvironment. Excessive IL-6 has been demonstrated in primary breast tumors and breast cancer patient sera and is associated with poor clinical outcomes in breast cancer. These clinical associations are corroborated by emerging preclinical data revealing that IL-6 is a potent growth factor and promotes an epithelial-mesenchyme (EMT) phenotype in breast cancer cells to indicate that IL-6 in the breast tumor microenvironment is clinically relevant. RESULTS: High serum levels of interleukin-6 correlate with poor outcome in breast cancer patients. However, few data are yet available on the relationship between IL-6 and stem/progenitor cells, which may fuel the genesis of breast cancer in vivo. Mammospheres (MS) from node invasive breast carcinoma tissues express IL-6 mRNA at higher levels than MS from matched non-neoplastic mammary glands. IL-6 mRNA is detectable only in basal-like breast carcinoma tissues; our results reveal that IL-6 triggers a Notch-3-dependent upregulation of the Notch ligand Jagged-1, whose interaction with Notch-3 promotes the growth of MS and Michigan Cancer Foundation-7 (MCF-7)-derived spheroids. IL-6 induces a Notch-3-dependent upregulation of the carbonic anhydrase IX gene and promotes a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. CONCLUSIONS: In conclusion, our data support the hypothesis that IL-6 induces malignant features in Notch-3-expressing, stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Regulação Neoplásica da Expressão Gênica , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Microambiente Tumoral , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Interleucina-6/genética , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor Notch3 , Receptores Notch/genética , Receptores Notch/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
Epidemiol Prev ; 39(3 Suppl 1): 40-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26405775

RESUMO

This annual survey, conducted by the Italian group for mammography screening (GISMa), collects individual data on diagnosis and treatment of about 50% of screen-detected, operated lesions in Italy. The 2011-2012 results show good overall quality and an improving trend over time. A number of critical issues have been identified, including waiting times (which have had a worsening trend over the years) and compliance with the recommendation of not performing frozen section examination on small lesions. Pre-operative diagnosis improved constantly over time, but there is still a large variation between Regions and programmes. For almost 90% of screen-detected invasive cancers a sentinel lymph node (SLN) biopsy was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN dissection for ductal carcinoma in situ, although apparently starting to decline, deserves further investigation. The detailed results have been distributed, among other ways by means of a web-based data-warehouse, to regional and local screening programmes, in order to allow multidisciplinary discussion and identification of the appropriate solutions to any issues documented by the data. The problem of waiting times should be assigned priority. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making monitoring effective in producing quality improvements with shorter waiting times.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/terapia , Mamografia , Auditoria Médica , Axila/cirurgia , Detecção Precoce de Câncer , Feminino , Inquéritos Epidemiológicos , Humanos , Itália , Programas de Rastreamento , Pessoa de Meia-Idade , Fatores de Risco , Biópsia de Linfonodo Sentinela , Fatores de Tempo
8.
J Cell Physiol ; 229(11): 1595-606, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24604522

RESUMO

Cancer stem cells (CSCs) are affected by the local micro-environment, the niche, in which inflammatory stimuli and hypoxia act as steering factors. Here, two nuclear receptors (NRs) agonists, i.e. pioglitazone (PGZ), a ligand of peroxisome proliferator activated receptor-γ, and 6-OH-11-O-hydroxyphenanthrene (IIF), a ligand of retinoid X receptors, were investigated for their capability to interference with the cross-talk between breast CSCs and the niche compartment. We found that IIF potentiates the ability of PGZ to hamper the mammospheres-forming capability of human breast tumours and MCF7 cancer cells, reducing the expression of CSCs regulatory genes (Notch3, Jagged1, SLUG, Interleukin-6, Apolipoprotein E, Hypoxia inducible factor-1α and Carbonic anhydrase IX). Notably, these effects are not observed in normal-MS obtained from human breast tissue. Importantly, NRs agonists abolish the capability of hypoxic MCF7 derived exosomes to induce a pro-inflammatory phenotype in mammary glands fibroblasts. Moreover, NRs agonist also directly acts on breast tumour associated fibroblasts to downregulate nuclear factor-κB pathway and metalloproteinases (MMP2 and MMP9) expression and activity. In conclusion, NRs agonists disrupt the inflammatory cross-talk of the hypoxic breast CSCs niche.


Assuntos
Neoplasias da Mama/patologia , Inflamação/patologia , Células-Tronco Neoplásicas/patologia , PPAR gama/metabolismo , Receptor Cross-Talk , Receptores X de Retinoides/metabolismo , Nicho de Células-Tronco , Antígenos de Neoplasias/metabolismo , Apolipoproteínas E/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/enzimologia , Anidrase Carbônica IX , Anidrases Carbônicas/metabolismo , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/metabolismo , Ligantes , Células MCF-7 , Metaloproteinase 9 da Matriz/metabolismo , Modelos Biológicos , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/enzimologia , Fenantrenos/farmacologia , Pioglitazona , Receptor Cross-Talk/efeitos dos fármacos , Receptores X de Retinoides/agonistas , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Nicho de Células-Tronco/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia , Tiazolidinedionas/farmacologia
9.
Am J Pathol ; 183(5): 1688-1697, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24036252

RESUMO

Cancer stem cell survival relies on the activation of inflammatory pathways, which is speculatively triggered by cell autonomous mechanisms or by microenvironmental stimuli. Here, we observed that hypoxic bone marrow stroma-derived transforming growth factor-ß 1 promotes the growth of human breast cancer stem cells as mammospheres. The ensuing Slug-dependent serine 139 phosphorylation of the DNA damage sensor H2AX in breast cancer stem cells induces tumor necrosis factor-α and IL-8 mRNAs, whose stability is enhanced by cytoplasmic ß-catenin. ß-Catenin also up-regulates and binds miR-221, reducing the stability of the miR-221 targets Rad51 and ERα mRNAs. Our data show that the Slug/ß-catenin-dependent activation of DNA damage signaling triggered by the hypoxic microenvironment sustains the proinflammatory phenotype of breast cancer stem cells.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Inflamação/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição/metabolismo , beta Catenina/metabolismo , Comunicação Autócrina/efeitos dos fármacos , Comunicação Autócrina/genética , Neoplasias da Mama/genética , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Citocinas/genética , Citocinas/metabolismo , Dano ao DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Inflamação/genética , Células MCF-7 , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Modelos Biológicos , Células-Tronco Neoplásicas/efeitos dos fármacos , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Serina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Transcrição da Família Snail , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Fator de Crescimento Transformador beta1/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Eur J Surg Oncol ; 50(7): 108351, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38701582

RESUMO

INTRODUCTION: Neoadjuvant chemotherapy (NAC) has a profound impact on surgical management of breast cancer. For this reason, the Italian Association of Breast Surgeons (ANISC) promoted the third national Consensus Conference on this subject, open to multidisciplinary specialists. MATERIALS AND METHODS: The Consensus Conference was held on-line in November 2022, and after an introductory session with five core-team experts, participants were asked to vote on eleven controversial issues, while results were collected in real-time with a polling system. RESULTS: A total of 164 dedicated specialists from 74 Breast Centers participated. Consensus was reached for only three of the eleven issues, including: 1) the indication to assess the response with Magnetic Resonance Imaging (79 %); 2) the need to re-assess the biological factors of the residual tumor if present (96 %); 3) the possibility of omitting a formal axillary node dissection for cN1 patients if a pathologic Complete Response (pCR) was confirmed with analysis of one or more sentinel lymph nodes (82 %). The majority voted in favor of mapping both the breast and nodal lesions pre-NAC (59 %), and against the omission of sentinel lymph node biopsy in cN0 patients in the case of pathologic or clinical Complete Response (69 %). In cases of cT3/cN1+ tumors with pCR, only 8 % of participants considered appropriate the omission of Post-Mastectomy Radiation Therapy. CONCLUSION: There is still a wide variability in surgical approaches after NAC in the "real world". As NAC is increasingly used, multidisciplinary teams should be attuned to conforming their procedures to the rapid advances in this field.


Assuntos
Neoplasias da Mama , Excisão de Linfonodo , Terapia Neoadjuvante , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama/cirurgia , Feminino , Itália , Imageamento por Ressonância Magnética , Quimioterapia Adjuvante , Consenso , Biópsia de Linfonodo Sentinela , Neoplasia Residual , Axila
11.
Eur J Surg Oncol ; 50(2): 107954, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38217946

RESUMO

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Cirurgiões , Humanos , Feminino , Neoplasias da Mama/patologia , Metástase Linfática/patologia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela/métodos , Axila/patologia , Itália , Linfonodo Sentinela/patologia
12.
Diagnostics (Basel) ; 13(7)2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37046459

RESUMO

Liquid biopsy (LB) is an emerging diagnostic tool that analyzes biomarkers in the blood (and possibly in other body fluids) to provide information about tumor genetics and response to therapy. This review article provides an overview of LB applications in human cancer with a focus on breast cancer patients. LB methods include circulating tumor cells and cell-free tumor products, such as circulating tumor DNA. LB has shown potential in detecting cancer at an early stage, monitoring tumor progression and recurrence, and predicting patient response to therapy. Several studies have demonstrated its clinical utility in breast cancer patients. However, there are limitations to LB, including the lack of standardized assays and the need for further validation. Future potential applications of LB include identifying the minimal residual disease, early detection of recurrence, and monitoring treatment response in various cancer types. LB represents a promising non-invasive diagnostic tool with potential applications in breast cancer diagnosis, treatment, and management. Further research is necessary to fully understand its clinical utility and overcome its current limitations.

13.
Ann Surg ; 255(5): 976-80, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22415419

RESUMO

OBJECTIVE: The goal of our study was to evaluate the sensitivity and specificity of sentinel lymph node biopsy (SLNB) frozen section (FS) examinations to detect metastatic lymph nodes and also its potential role in avoiding unnecessary demolitive axillary surgery. BACKGROUND: SLNB is the standard of care in surgical oncology of the breast. Intraoperative evaluation of the SLN seems to achieve sufficient sensitivity for macrometastasis (Ma), leading to axillary lymph node dissection (ALND) only when strictly necessary. Is it equally as clear when to perform ALND if micrometastasis (Mi) or isolated tumor cells (ITCs) are detected? METHODS: All consecutive patients from January 2005 to September 2010 operated on for breast cancer were prospectively enrolled. All patients underwent an FS SLNB. The sensitivity and specificity of SLN FSs in detecting Ma, Mi, and ITCs was calculated. All patients with Ma or Mi at FS underwent ALND. For all patients who underwent ALND, the number of metastatic non-SLNs was recorded and correlated to the size of the SLN metastasis. RESULTS: A total of 753 patients were enrolled. FS examination had an overall 54% sensitivity and 100% specificity in detecting metastatic disease (Ma/Mi/ITCs). The sensitivity rises to 89% if only Mas were considered and to 64% if Mas and Mis were counted together. All patients with Mas or Mis detected at FS had a completion ALND during the same procedure (156/222). All patients with Mas detected at final pathology (16 false negatives, 2.6%) and 50 women with Mis or ITCs (119 false negatives, 20%) underwent a delayed ALND. When Mis or ITCs were detected in the SLN, only 8 of 73 (10.9%) and none of 4 (0%) patients, respectively, had at least 1 metastatic non-SLN after ALND. Two patients (2/460, 0.43%) who had negative SLNs showed local axillary recurrence. After a mean follow-up of 32 months, none of the 71 patients with Mis or ITCs who did not undergo a second operation showed local recurrence. CONCLUSIONS: SLNB FS is highly effective in detecting the subgroup of patients who may benefit from completion ALND during the same surgical procedure. The role of Mi/ITCs in the SLN(s) is still unclear, but our data lean toward a less aggressive surgical approach.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Biópsia de Linfonodo Sentinela , Axila/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Feminino , Secções Congeladas , Humanos , Período Intraoperatório , Excisão de Linfonodo , Metástase Linfática/diagnóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Padrão de Cuidado
14.
Epidemiol Prev ; 36(6 Suppl 1): 87-95, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23293273

RESUMO

This survey, conducted by the Italian breast screening network (GISMa), collects yearly individual data on diagnosis and treatment on about 50% of all screen-detected, operated lesions in Italy. The 2010 results show good overall quality and an improving trend over time. Critical issues were identified, including waiting times and compliance with the recommendations on not performing frozen section examination on small lesions. Preoperative diagnosis improved constantly over the years, but there is still a large variation between regions and programmes. For almost 90% of screen-detected invasive cancers the sentinel lymph node technique (SLN) was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN for ductal carcinoma in situ deserves further investigation. The detailed results have been distributed, also by means of a web data warehouse, to regional and local screening programmes in order to allow multidisciplinary discussion and identification of the appropriate solutions to any issues documented by the data. It should be assigned priority to the problem of waiting times. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making monitoring effective in producing quality improvements with shorter waiting times.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Detecção Precoce de Câncer/normas , Mamografia , Programas de Rastreamento/normas , Auditoria Médica , Indicadores de Qualidade em Assistência à Saúde , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/terapia , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela
15.
Cancers (Basel) ; 14(6)2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35326578

RESUMO

The preservation of fertility in cancer patients is a crucial aspect of modern reproductive medicine. Amenorrhea and infertility often occur after cancer therapy, worsening the quality of life. Cryopreservation of oocytes in young cancer patients is a therapeutic option for preserving fertility. A prospective study was conducted on 508 cancer patients who underwent oocyte cryopreservation to preserve fertility between 1996 and 2021 including the COVID-19 pandemic period. Patients underwent ovarian stimulation, followed by egg retrieval, and oocytes were cryopreserved by slow freezing or vitrification. Sixty-four thawing/warming cycles were performed. Survival, fertilization, pregnancy, and birth rate over the thawing/warming cycles were obtained. The data were compared with those from a group of 1042 nononcological patients who cryopreserved supernumerary oocytes. An average of 8.8 ± 6.9 oocytes were retrieved per cycle, and 6.1 ± 4.2 oocytes were cryopreserved. With their own stored oocytes, 44 patients returned to attempt pregnancy. From a total of 194 thawed/warmed oocytes, 157 survived (80%). In total, 100 embryos were transferred in 57 transfer/cycles, and 18 pregnancies were achieved. The pregnancy rate per transfer and pregnancy rate per patient were 31% and 41%, respectively. No statistically significant differences were observed between oncological patients and nononcological patients. A total of 15 babies were born from oncological patients. Children born showed normal growth and development. One minor malformation was detected.

16.
Genome Biol ; 23(1): 177, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35996163

RESUMO

BACKGROUND: Dyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. In humans, its defective function is associated with cancer development and induces specific post-transcriptional alterations of gene expression. In this study, we seek to unbiasedly identify mRNAs regulated by dyskerin in human breast cancer-derived cells. RESULTS: We find that dyskerin depletion affects the expression and the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin in the cytoplasm in the form of shorter 3' snoRT fragments. We then characterize the whole cytoplasmic dyskerin RNA interactome and find both H/ACA box snoRTs and protein-coding transcripts which may be targeted by the snoRTs' guide properties. Since a fraction of these protein-coding transcripts is involved in the nuclear hormone receptor binding, we test to see if this specific activity is affected by dyskerin. Obtained results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer cells. These results are paralleled by consistent observations on the outcome of primary breast cancer patients stratified according to their tumor hormonal status. Accordingly, experiments in nude mice show that the reduction of dyskerin levels in estrogen-dependent cells favors xenograft development in the absence of estrogen supplementation. CONCLUSIONS: Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions.


Assuntos
Neoplasias da Mama , Proteínas de Ciclo Celular , Proteínas Nucleares , RNA Nucleolar Pequeno , Receptores Citoplasmáticos e Nucleares , Animais , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Citoplasma , Estrogênios , Feminino , Humanos , Camundongos , Camundongos Nus , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Mensageiro/genética , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Proteínas de Ligação a RNA , Receptores Citoplasmáticos e Nucleares/metabolismo
17.
Epidemiol Prev ; 35(5-6 Suppl 5): 87-95, 2011.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-22166352

RESUMO

This survey, conducted by the Italian breast screening network (GISMa), collects individual data yearly on about 50% of all screen-detected, operated lesions in Italy. The 2008-2009 results show good overall quality of diagnosis and treatment and an improving trend over time. Critical issues were identified, including waiting times and compliance with the recommendations on not performing frozen section examination on small lesions. Pre-operative diagnosis reached the acceptable target, but there is a large variation between regions and programmes. For almost 90% of screen-detected invasive cancers the sentinel lymph node technique (SLN) was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed, also by means of a web-based data warehouse, to regional and local screening programmes in order to allow multidisciplinary discussion and identification of the appropriate solutions to any problem documented by the data. Specialist breast units with adequate case volume and enough resources would provide the best setting for making audits effective in producing quality improvements with shorter waiting times.


Assuntos
Axila/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Detecção Precoce de Câncer/normas , Auditoria Médica , Biópsia de Linfonodo Sentinela , Neoplasias da Mama/epidemiologia , Feminino , Secções Congeladas , Fidelidade a Diretrizes , Inquéritos Epidemiológicos , Humanos , Itália/epidemiologia , Resultado do Tratamento
18.
Eur J Surg Oncol ; 47(2): 240-244, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32962889

RESUMO

INTRODUCTION: Pre-analytics involves handling and processing of microbiopsy and surgical specimen. It is critical for the preservation of morphology and the integrity of molecular markers, which are paramount as prognostic and predictive factors in breast cancer. Although pre-analytical variables in breast cancer are codified by national and international guidelines, there is currently no data on their actual endorsement in clinical practice among Breast Units (BU). MATERIALS AND METHODS: An anonymous questionnaire was sent by e-mail by Senonetwork Italia, a no-profit organization representing the multidisciplinary network of BU in Italy. The questionnaire involved twenty-four questions concerning critical issues related to the average time and transport temperature of the samples, monitoring of warm and cold ischemia, average fixation time for biopsies and surgical specimens, inking of the margins, and radiography of the operating sample. RESULTS: Forty-nine of 113 affiliated BU (43%), involved in the management of 44% of all breast cancer treated every year in Italy, answered the questionnaire. More than 90% of the BU reported a biopsy/VABB fixation time between 6 and 24 h. Only 41% of the Centers received the fresh operative sample to be sectioned immediately, 20% used the vacuum method and the sample arrived in the laboratory within 24-72 h. Delay in sectioning the sample was reported in as many as 40% of BU, while hot and cold ischemia time was monitored in only 4.2% and 6.2% of BU, respectively. CONCLUSION: Critical issues on pre-analytics are reported by the majority of dedicated BU in Italy. This represents a major challenge regarding quality of care, and improvements are needed in order to obtain valid and reproducible results of prognostic and predictive factors.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Manejo de Espécimes/métodos , Biópsia , Feminino , Humanos , Incidência , Itália/epidemiologia , Inquéritos e Questionários
19.
J Cancer Res Clin Oncol ; 147(2): 507-516, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33236215

RESUMO

PURPOSE: In daily practice, a contralateral breast cancer (CBC) is usually considered as a new independent tumor despite the indications of several studies showing that the second neoplasia may be a metastatic spread of the primary tumor. Recognition of clonal masses in the context of multiple synchronous or metachronous tumors is crucial for correct prognosis, therapeutic choice, and patient management. Mitochondrial DNA (mtDNA) sequencing shows high informative potential in the diagnosis of synchronous neoplasms, based on the fact that somatic mtDNA mutations are non-recurrent events, whereas tumors sharing them have a common origin. We here applied this technique to reveal clonality of the CBC with respect to the first tumor. METHODS: We analyzed 30 sample pairs of primary breast cancers and synchronous or metachronous CBCs with detailed clinical information available and compared standard clinico-pathological criteria with mtDNA sequencing to reveal the metastatic nature of CBCs. RESULTS: MtDNA analysis was informative in 23% of the cases, for which it confirmed a clonal origin of the second tumor. In addition, it allowed to solve two ambiguous cases where histopathological criteria had failed to be conclusive and to suggest a clonal origin for two additional cases that had been classified as independent by pathologists. CONCLUSION: Overall, the mtDNA-based classification showed a more accurate predictive power than standard histopathology in identifying cases of metastatic rather than bilateral breast cancers in our cohort, suggesting that mtDNA sequencing may be a more precise and easy-to-use method to be introduced in daily routine to support and improve histopathological diagnoses.


Assuntos
Neoplasias da Mama/patologia , DNA Mitocondrial/genética , Mutação , Segunda Neoplasia Primária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sequência de DNA
20.
Eur J Surg Oncol ; 47(8): 1913-1919, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33972142

RESUMO

RATIONALE: On October 15th, 2020, the first Surgical National Consensus Conference on neoadjuvant chemotherapy (NACT) was promoted by the Italian Association of Breast Surgeons (ANISC). METHOD: The Consensus Conference was entirely held online due to anti-Covid-19 restrictions and after an introductory four lectures held by national and international experts in the field, a total of nine questions were presented and a digital "real-time" voting system was obtained. A consensus was reached if 75% or more of all panelists agreed on a given question. RESULTS: A total of 202 physicians, from 76 different Italian Breast Centers homogeneously distributed throughout the Italian country, participated to the Conference. Most participants were surgeons (75%). Consensus was reached for seven out of the nine considered topics, including management of margins and lymph nodes at surgery, and there was good correspondence between the 32 "Expert Panelists" and the "Participants" to the Conference. Consensus was not achieved regarding the indications to NACT for high-grade luminal-like breast tumors, and the need to perform an axillary lymph node dissection in case of micrometastases in the sentinel lymph node after NACT. CONCLUSIONS: NACT is a topic of major interest among surgeons, and there is need to develop shared guidelines. While a Consensus was obtained for most issues presented at this Conference, controversies still exist regarding indications to NACT in luminal B-like tumors and management of lymph node micrometastases. There is need for clinical studies and analysis of large databases to improve our knowledge on this subject.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Ensaios Clínicos como Assunto , Feminino , Humanos , Itália , Excisão de Linfonodo , Metástase Linfática , Margens de Excisão , Mastectomia , Gradação de Tumores , Micrometástase de Neoplasia/terapia , Estadiamento de Neoplasias , Seleção de Pacientes , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/metabolismo , Carga Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA